The reverse effect on drug-resistance against tyrosine kinase inhibitor STI571 in mdr1 and bcr-abl positive leukemic cells.
- Author:
Li CHEN
1
;
Jian-Min WANG
;
Xiao-Ping XU
;
Lei GAO
;
Xin-Hong FEI
;
Jing-Wei LOU
;
Zheng-Xia HUANG
Author Information
1. Department of Hematology, Changhai Hospital of The Second Military Medical University, Shanghai 200433, China.
- Publication Type:Journal Article
- MeSH:
Antineoplastic Agents;
pharmacology;
Benzamides;
Cyclosporine;
pharmacology;
Drug Resistance, Neoplasm;
Genes, MDR;
Genes, abl;
Humans;
Imatinib Mesylate;
Interferon-alpha;
pharmacology;
K562 Cells;
Leukemia;
drug therapy;
genetics;
Piperazines;
pharmacology;
Pyrimidines;
pharmacology;
Tamoxifen;
pharmacology
- From:
Journal of Experimental Hematology
2003;11(6):600-603
- CountryChina
- Language:Chinese
-
Abstract:
To explore the possibility of leukemia cell line of both bcr-abl and mdr-1 positive were cross-resistant to tyrosine kinase inhibitor STI571 and its reversal way, the inhibitory effect of STI571 on K562-n/VCR cells was detected with MTT method and reverse effects of CsA, TAM, IFN-alpha and CsA cominated with IFN-alpha were observed. The results showed that K562-n/VCR cell line expressing bcr-abl and mdr1 positive was resistant to STI571, and could be reversed by 5.18, 1.82 and 1.67-fold respectively, when treated with CsA, TAM, and IFN-alpha. It could be reversed by 34.87-fold with combination of half-dose CsA and IFN-alpha. In conclusion, amplification of mdr1 gene may contribute to drug-resistance of bcr-abl positive leukemic cells against STI571. The reversal agents, CsA, TAM and IFN-alpha show obviously reverse effects on drug-resistance. The combination of half-dose of both CsA and IFN-alpha display stronger effect than the full dose of either.